The objective of this project is to utilize the canine distemper complex as a model to study the pathogenesis of virus-induced demyelinating encephalitis as it occurs in association with subacute sclerosing panencephalitis (SSPE) and perhaps with multiple sclerosis (MS). The etiologic link between SSPE and persistent measles virus infection (a paramyxovirus infection as canine distemper) has been firmly established. Evidence is accumulating that MS may also be a virus-induced demyelinating encephalitis. The process of demyelination, often characterized by remissions and relapses probably depends upon a persistent infection and an interplay between host and agent whereby immunological factors play a key role. The availability of a canine distemper virus isolate capable of producing demyelinating encephalitis without preceeding respiratory disease, permits careful dissection of individual mechanisms and their importance for the production of this disease. Acute and chronic studies in gnotobiotic pups are proposed together with specifically designed in vivo and in vitro models to determine the unique characteristics of this isolate and the immune responses which permit persistence of the agent in the brain and lead to selective myelin destruction. The role of specific enzymes responsible for myelin catabolism and their specific activation will be explored. It will be further determined to what extent viral transcription alters the antigenic composition of cellular membranes from persistently infected cells and how this alteration may relate to the demyelinating process. It is conceivable that pathogenetic principles established in this model may be partly, if not fully, applicable to multiple sclerosis.